Ignite Creation Date:
2024-05-05 @ 12:01 PM
Last Modification Date:
2024-10-26 @ 9:18 AM
Study NCT ID:
NCT00214890
Status:
COMPLETED
Last Update Posted:
2021-09-24
First Post:
2005-09-20
Brief Title:
Viral Dynamics and Pharmacokinetics of Abacavir and Tenofovir
Sponsor:
University of California San Diego
Organization:
University of California San Diego
Study Overview
Official Title:
CCTG584 Viral Dynamics and Pharmacokinetics of Tenofovir and Abacavir Monotherapy Versus the Combination Therapy of TDF-ABC in HIV-Infected Treatment Naive Patients
Status:
COMPLETED
Status Verified Date:
2021-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Once-daily nucleotidenucleoside reverse transcriptase inhibitor NtRTINRTI combinations form the backbone of many regimens Although efficacy data exists between tenofovir and the pyrimidine analogues ie lamivudine and emtricitabine recent clinical data suggests a potential interaction between tenofovir and purine analogs ie abacavir and didanosine
Specific Aim 1 To evaluate the impact of an acyclic nucleoside phosphonate tenofovir TDF on the intracellular metabolism of a purine nucleoside analog abacavir ABC as a determinant of the antiviral potency of this nucleotidenucleoside reverse transcriptase inhibitor NtRTINRTI combination
Hypothesis 1 ABC and TDF dosed together will have reduced antiviral activity as measured by early plasma HIV RNA decay kinetics than the drugs given alone
Hypothesis 2 ABC dosed with TDF will have reduced intracellular concentrations as measured by the ratio of carbovir triphosphate active metabolite of ABC to deoxyguanosine triphosphate endogenous nucleotide compared to ABC given alone
Specific Aim 1 To evaluate the impact of an acyclic nucleoside phosphonate tenofovir TDF on the intracellular metabolism of a purine nucleoside analog abacavir ABC as a determinant of the antiviral potency of this nucleotidenucleoside reverse transcriptase inhibitor NtRTINRTI combination
Hypothesis 1 ABC and TDF dosed together will have reduced antiviral activity as measured by early plasma HIV RNA decay kinetics than the drugs given alone
Hypothesis 2 ABC dosed with TDF will have reduced intracellular concentrations as measured by the ratio of carbovir triphosphate active metabolite of ABC to deoxyguanosine triphosphate endogenous nucleotide compared to ABC given alone
Detailed Description:
The primary objectives of this study are to compare the virologic potency and pharmacology of TDF and ABC alone and in combination Since it is not feasible or ethical to give mono or dual-therapy with these agents for prolonged intervals this project was designed to take advantage of a short term drug exposure The study performs intensive lab monitoring with a cross-over design to compare short courses of monotherapy and dual-therapy This is an open-labeled study of a dual NRTINtRTI combination ABC TDF compared to ABC and TDF monotherapy administered for 7 days A screening genotype will be done to confirm that there are no resistance-associated mutations at baseline Each subject will then be randomized to a 7-day sequence of monotherapy ABC or TDF and four measurements for plasma HIV RNA will be done to calculate the slope of the phase one viral decay Prior to initiation of nucleoside analogues PBMCs will be collected to measure baseline expression of nucleoside transport enzymes via RT-PCR and Western blot analysis On days 7 and 8 serial blood specimens will be collected for plasma and intracellular levels of TDF and ABC The monotherapy sequence will be followed by a 35-day washout period
After the washout day 42 subjects will initiate the dual NRTINtRTI therapy sequence for an additional 7 days During dual NRTINtRTI therapy again four measurements for HIV RNA will be done to calculate the slope of the phase one viral decay On day 48 and 49 serial plasma and intracellular levels of ABC TDF will be evaluated On Day 49 a second HIV genotype will be performed in real time On day 49 after the second 7-day sequence all subjects will receive EFV in addition to the ABC TDF combination for 14 days Afterwards a second sample of PBMCs will be collected to evaluate for a potential induction or suppression of nucleoside transport enzymes Since the long-term efficacy of the TDF ABC nucleoside backbone is not yet known TDF will be discontinued day 63 and 3TC will be substituted Subjects will then continue on the HAART portion of the study for an additional 46 weeks of EFV ABC 3TC
After the washout day 42 subjects will initiate the dual NRTINtRTI therapy sequence for an additional 7 days During dual NRTINtRTI therapy again four measurements for HIV RNA will be done to calculate the slope of the phase one viral decay On day 48 and 49 serial plasma and intracellular levels of ABC TDF will be evaluated On Day 49 a second HIV genotype will be performed in real time On day 49 after the second 7-day sequence all subjects will receive EFV in addition to the ABC TDF combination for 14 days Afterwards a second sample of PBMCs will be collected to evaluate for a potential induction or suppression of nucleoside transport enzymes Since the long-term efficacy of the TDF ABC nucleoside backbone is not yet known TDF will be discontinued day 63 and 3TC will be substituted Subjects will then continue on the HAART portion of the study for an additional 46 weeks of EFV ABC 3TC
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None